Pharmacology of the Eye Flashcards
Pupillary Response
Three muscles involved in pupil size (iris movement):
-
Dilator muscles in the iris (more outside portion of the iris)
- Fibers of this muscle are arranged radially
- Mostly α-adrenergic
- Contraction ⇒ pupil dilation
-
Pupillary sphincter muscles
- Circular band around the iris
- Have cholinergic receptors
- Contraction ⇒ pupil constriction
-
Ciliary muscles ⇒ located in the ciliary body
Two actions to provide for accommodation:- ⊕ with cholinergic agents ⇒ contraction ⇒ near vision
- ⊕ with adrenergic activity (mostly β) ⇒ relaxation ⇒ far vision
Horner’s Syndrome
Clinical Manifestations
↓ SNS stimulation to the eye
- Unequal pupils (ipsilateral pupil dilated) ⇒ anisocoria
-
Ipsilateral lid ptosis
- SNS innervates the superior tarsal muscle (Muller’s muscle)
-
Ipsilateral eyebrow is raised
- Pt using voluntary facial muscles to keep the eye open
-
Irises are different colors (right is a few shades lighter than left)
- ↓ SNS stimulation to melanocytes
- Suggests condition has been there for at least a few years or is congenital
Horner’s Syndrome
Pathophysiology
Hypothalamus (1st order neuron) ⇒ synapses around C8/T1 of spinal cord (2nd order neuron) ⇒ apex of the lung ⇒ under the subclavian artery ⇒ superior cervical ganglion (3rd order neuron) ⇒ eye ⇒ pupillary dilator muscle, Muller’s muscles, and ciliary muscle
- Congenital Horner’s is benign
- 50% of blockages in 1st or 2nd order sympathetics causing Horner’s are associated with tumors
- Tumor in the apex of the lung ⇒ Pancoast tumor
- Horner’s arising from a 3rd order deficit is usually not associated with tumor
Horner’s Syndrome
Clinical Evaluation
To test for Horner’s:
-
Cocaine
- ⊗ NE re-uptake ⇒ ↑ existing stimulation
- Administer a drop of 10% solution of cocaine in each eye
- Normal eye ⇒ pupil dilation as expected
-
Affected eye ⇒ no effect
- No NE being released, so cocaine blocks reuptake of nothing
-
Apraclonidine may also be used
- α2 adrenergic agonist with weak α1 activity
- Receptors in effected eye are supersensitive
- Affected eye ⇒ pupil dilation
- Normal eye ⇒ no effect
-
Hydroxyamphetamine (Paredrine)
- Indirect α-adrenergic agonist ⇒ ↑ release of NE ⇒ dilation
- Differentiate 1st and 2nd order from 3rd order Horner’s
- Only 3rd order neurons are stimulated by eye drops
- Will cause pupil dilation in normal and affected eye except with 3rd order defects
Horner’s Syndrome vs Physiologic Anisocoria
Horner’s Syndrome vs Physiologic anisocoria (20% of all people)
- Look at lid position ⇒ down in eye with smaller pupil ⇒ Horner’s syndrome possible
-
Stimulate SNS via light reflex ⇒ pupil dilation
- Physiologic anisocoria ⇒ both pupils dilate ⇒ pupils “equally unequal”
- Difference in size will remain constant
- Horner’s ⇒ only normal pupil dilates ⇒ difference in size will increase in dim ligh
- Then do cocaine/hydroxyamphetamine (Paredrine) tests
- Physiologic anisocoria ⇒ both pupils dilate ⇒ pupils “equally unequal”
Mydriasis
Etiologies
↓ PNS stimulation ⇒ ↑ pupil size
-
Adie’s (tonic) pupil
- 70% of cases in young women from teens to 30’s
- 50-90% of these pts will have ↓ DTRs
- Pupil very slow to constrict and very slow to dilate in response to light
- Usually caused by damage to the post-ganglionic parasympathetic fibers (from the ciliary ganglion to the iris)
- May be seen in headaches, viruses, etc.
- Is benign but need to be able to diagnose it
- 70% of cases in young women from teens to 30’s
-
Iris damage (due to trauma)
- Smaller or larger pupil can be abnormal
-
Pharmacologic dilation of one eye
- Deliberate or inadvertent inoculation with pharmacological dilators
- Exposure to Jimson weed (contains bella donna alkaloids, an atropine-like substance)
- Transdermal patches used for travel sickness prevention (scopolamine)
-
Third nerve palsy
- Efferent fibers from the Edinger-Westphal nucleus come through CN-III to the pupillary sphincter
Mydriasis
Clinical Evaluation
Pilocarpine ⇒ ⊕ PNS ⇒ pupil constriction
-
⅛% Pilocarpine solution
- Too weak to constrict a normal pupil
- Adie’s pupil ⇒ denervation hypersensitivity ⇒ pupil constriction by 1/8 ⅛% Pilocarpine
- Takes some time to develop
-
1% Pilocarpine solution
- Contricts all pupils that are not pharmacologically dilated
- B/l constriction r/o pharmacological dilation ⇒ suspect CN III palsy
Anisocoria
Diagnosis
Cycloplegic Agent
Relaxes accommodation / Relaxes pupillary constriction
Mydriatic Agent
Dilates pupil
Dilating Drops
-
Cholinergic antagonists ⇒ ⊗ effects of ACh @ muscarinic receptors on the iris and ciliary body
- Do not actively dilate the pupil
- Relax constriction and accommodation
-
Drugs include:
- Atropine
- Tropicamide
- Cyclopentolate
- Homatropine
- Scopolamine
-
Sympathetic agonists ⇒ ⊕ effects of NE @ adreneric receptors on the iris and ciliary body
- Activates dilation
-
Drugs include:
- Phenylephrine
REMEMBER TO DO THE FLASHLIGHT TEST TO CHECK FOR NARROW ANTERIOR CHAMBER ANGLES BEFORE YOU DILATE PATIENTS ‘ EYES.
Atropine
- Naturally occurring alkaloid first isolated from the belladonna plant
- The most potent dilating drug
- Effects can last two weeks
-
Used when long-term dilation is necessary
- Very bad iritis or uveitis
- Following eye surgery
Tropicamide
(Mydriacyl)
- Fastest acting ⇒ max effect in ~ 30 mins
- Shortest duration of action ⇒ lasts 4-6 hours
- 0.5% used for fundus exams
- Adequate to use when determining refraction errors in children
Cyclopentolate
(Cyclogyl)
- Slightly stronger than Tropicamide
- Lasts up to 24 hours
- Given several times per day for prolonged effect
-
Indications:
- Used in children to determine accurate refraction correction
-
Corneal abrasions
- Pain ass. w/ corneal abrasion d/t ciliary muscle spasm,
- Pupil dilation and relaxing accommodation will make the pt more comfortable
- Mild conditions where you want the eye relaxed for a few days
Homatropine
- Effects last 1-3 days
-
Prescribed 4x/day for:
- Corneal abrasions
- Chemical burns to the eyes
- Iritis or uveitis
- Post-operatively
Scopolamine
- Lasts 2-4 days to ~ a week
-
Greater incidence of toxic reactions than any of the other drugs
- Psychosis, restlessness, confusion, hallucinations, vomiting, urinary incontinence.
- Not used on a regular basis
- Useful when applied as a transdermal patch to prevent motion sickness
- In this use, it may cause pupillary dilation
Phenylephrine
(Neosynephrine)
Adrenergic agonist ⇒ ⊕ SNS stimulation
-
2.5% solution
-
⊕ dilator muscles
- Dilation seen in ~ 45 mins
- Recovers in ~ 6 hours
-
Vasoconstriction
- Added in small concentration to OTC drops (e.g. Visine_
- Whitens the eye via vasoconstrictor property
- Several hours after use ⇒ rebound effect ⇒ vasodilation and redder eyes
- ⊕ Muller’s muscles ⇒ eyes open wide
-
⊕ dilator muscles
-
10% solution
- Follows the tear route into nasal cavity and absorbed by vasculature there
- Should never used ⇒ can cause death with just a few drops
- Hypertensive crisis, occipital headaches, ventricular arrhythmias, tachycardia
Intraocular Fluid
Pathway
Ciliary bodies ⇒ posterior chamber ⇒ pupil ⇒ anterior chamber ⇒ trabecular meshwork ⇒ canal of Schlemm’s ⇒ episcleral vein ⇒ aqueous vein ⇒ blood
Glaucoma
Overview
Defined as intraocular pressure high enough to cause ocular damage
Pressure above normal but not high enough to cause ocular damage ⇒ ocular hypertension
- ↓ outflow causes 95% of glaucoma
- Overproduction of aqueous humor causes 5% of glaucoma
- Optic nerve is the most sensitive to ↑ IOP
- Pressure starts to eat away at the nerve fibers
- Opthalomoscopic picture of this is an enlarged optic cup
Open Angle Glaucoma
95% of Glaucoma cases
Caused by decrease outflow of aqueous humor
Diagnosis:
- Measure intraocular pressure
- Examine the optic nerve
- Look at peripheral vision, which is usually affected first
Angle-closure Glaucoma
(Narrow Angle Glaucoma)
Caused by increased production of aqueous humor
Seen in < 5% of Glaucoma cases
- Type of glaucoma you must look out for when dilating pupils
-
Acute attacks can result from sympathetic stimulation
- Lens starts to swell and gets cataracts
- Lens pushes the iris forward
- Pupil dilation ⇒ bunches the iris up ⇒ sudden absolute closure of the trabecular meshwork
- Pressure severely builds up within a couple hours ⇒ medical emergency
-
Clinical manifestations:
- Severe pain (first in the eyes, then headache)
- Redness of the sclera
- Nausea and vomiting
- Cloudy cornea
- Fixed, irregular, mid-dilated pupils
-
Treatment:
- Break initial attack with drops to ↓ pressure
- Small hole cut through the iris with a laser in less < 5 mins
- Creates opening to allow pressures between anterior and posterior chambers to equalize
- Lifetime cure and is done bilaterally
IOP Lowering
Drugs
- Pilocarpine
- Epinephrine
- Dipivefrin (Propine)
- Timolol / Betaxolol
- Latanoprost
- Dorzolamide
Pilocarpine
Direct-acting cholinergic agonist
-
Effects:
-
↓ IOP ⇒ desired effect
- Purposed mech: contracts and pulls iris in ⇒ stretch trabecular meshwork spaces ⇒ ↑ drainage of aqueous humor
- Pupillary constriction ⇒ side effect
- Spasm of accommodation ⇒ side effect
-
↓ IOP ⇒ desired effect
-
Indications:
- Glaucoma
- Testing for anisocoria
Epinephrine
Direct-acting alpha and beta agonist
-
Effects:
-
↓ Intraocular pressure
- By increasing outflow
- Conjunctival constriction
- Slight midriasis
-
↓ Intraocular pressure
-
Adverse effects:
- Via absorption into nasal vasculature
- Hypertensive crisis, tachycardia, etc.
- Localized burning and irritation
- Localized allergic reaction
- Accumulation of melanin granules
- Via absorption into nasal vasculature
Dipivefrin
(Propine)
More lipophilic version of epinephrine
-
Greater absorption through the cornea
- Major reduction of the systemic side effects
- 0.1% drug has equal effect to 2% epinephrine
- After absorption into the eye, it is transformed to epinephrine
- Works via receptors in the trabecular meshwork ⇒ ↑ outflow ⇒ ↓ IOP
- More frequently used today
Timolol
Non-selective β blocker
- More effective than epinephrine or pilocarpine
-
Drug of choice for glaucoma
- Works by ↓ aqueous formation via receptors on the ciliary body
-
Side effects:
- Localized irritation and burning
- CNS effects: lethargy, lightheadedness, fatigue, memory loss
- Cardiovascular effects: bradycardia, hypotension, syncope, arrhythmias, wheezing, pulmonary edema, congestive heart failure and death
- Timolol is expensive ⇒ different formulations were developed
Levobunolol
(Betagan)
Non-selective β blocker
↓ aqueous humor production ⇒ ↓ IOP
Betaxolol
β1 selective β blocker ⇒ cardioselective
- Limits its side effects
- Useful in pts with a hx of CHF, asthma or other conditions where β2 blockers are contraindicated
Latanoprost
Prostaglandin F2 alpha analog
- Widely used to treat glaucoma
- Thought to work by enhancing uveoscleral output of aqueous humor
- Unusual side effect of causing long eye lashes
Dorzolamide
Carbonic anhydrase inhibitor
⊗ CA in the ciliary body epithelium ⇒ ↓ bicarbonate ions ⇒ ↓ fluid transport ⇒ ↓ IOP
